PHARMACOKINETICS AND BIOAVAILABILITY OF A SUSTAINED-RELEASE DILTIAZEMFORMULATION (MONO-TILDIEM LP 300 MG) AFTER REPEATED ADMINISTRATION INHEALTHY-VOLUNTEERS

The usual dosage regimen of diltiazem (Tildiem) is 60 mg 3-4 times a d ay. A sustained-release formulation has been developed (Mono-Tildiem L P 300 mg) in order to allow a single daily administration. Two repeate d dosing studies were performed in healthy volunteers. The absolute bi oavailability of sustained-release diltiazem LP 300 mg was investigate d using concomitant i.v. administration of C-13-labelled drug: absolut e bioavailability of the ''once a day'' formulation was 35%. The secon d study compared sustained-release diltiazem LP 300 mg with the standa rd formulation of diltiazem. The results showed that the diltiazem pla sma concentrations obtained after the LP formulation remained stable b etween 2 and 14 h after administration and were compatible with a once a day administration. Relative bioavailability of sustained-release d iltiazem LP 300 mg was 79.3 % compared with diltiazem. Therefore, a un itary dose of sustained-release diltiazem LP 300 mg was chosen as the dose equivalent to the daily dose administered with the standard dilti azem formulation.